%T An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype %L discovery1536203 %P 322-329 %V 82 %J Biological Psychiatry %A N Direk %A S Williams %A JA Smith %A S Ripke %A T Air %A AT Amare %A N Amin %A BT Baune %A DA Bennett %A DH Blackwood %A D Boomsma %A G Breen %A HN Buttenschøn %A EM Byrne %A AD Børglum %A E Castelao %A S Cichon %A TK Clarke %A MC Cornelis %A U Dannlowski %A PL De Jager %A A Demirkan %A E Domenici %A CM van Duijn %A EC Dunn %A JG Eriksson %A T Esko %A JD Faul %A L Ferrucci %A M Fornage %A E de Geus %A M Gill %A SD Gordon %A HJ Grabe %A G van Grootheest %A SP Hamilton %A CA Hartman %A AC Heath %A K Hek %A A Hofman %A G Homuth %A C Horn %A J Jan Hottenga %A SL Kardia %A S Kloiber %A K Koenen %A Z Kutalik %A KH Ladwig %A J Lahti %A DF Levinson %A CM Lewis %A G Lewis %A QS Li %A DJ Llewellyn %A S Lucae %A KL Lunetta %A DJ MacIntyre %A P Madden %A NG Martin %A AM McIntosh %A A Metspalu %A Y Milaneschi %A GW Montgomery %A O Mors %A TH Mosley %A JM Murabito %A B Müller-Myhsok %A MM Nöthen %A DR Nyholt %A MC O'Donovan %A BW Penninx %A ML Pergadia %A R Perlis %A JB Potash %A M Preisig %A SM Purcell %A JA Quiroz %A K Räikkönen %A JP Rice %A M Rietschel %A M Rivera %A TG Schulze %A J Shi %A S Shyn %A GC Sinnamon %A JH Smit %A JW Smoller %A H Snieder %A T Tanaka %A KE Tansey %A A Teumer %A R Uher %A D Umbricht %A S Van der Auwera %A EB Ware %A DR Weir %A MM Weissman %A G Willemsen %A J Yang %A W Zhao %A H Tiemeier %A PF Sullivan %D 2017 %N 5 %O © Society of Biological Psychiatry, 2016. This manuscript version is made available under a Creative Commons Attribution Non-commercial Non-derivative 4.0 International license (CC BY-NC-ND 4.0). This license allows you to share, copy, distribute and transmit the work for personal and non-commercial use providing author and publisher attribution is clearly stated. Further details about CC BY licenses are available at https://creativecommons.org/licenses/. Access may be initially restricted by the publisher. %C United States %X BACKGROUND: The genetics of depression has been explored in genome-wide association studies that focused on either major depressive disorder or depressive symptoms with mostly negative findings. A broad depression phenotype including both phenotypes has not been tested previously using a genome-wide association approach. We aimed to identify genetic polymorphisms significantly associated with a broad phenotype from depressive symptoms to major depressive disorder. METHODS: We analyzed two prior studies of 70,017 participants of European ancestry from general and clinical populations in the discovery stage. We performed a replication meta-analysis of 28,328 participants. Single nucleotide polymorphism (SNP)-based heritability and genetic correlations were calculated using linkage disequilibrium score regression. Discovery and replication analyses were performed using a p-value-based meta-analysis. Lifetime major depressive disorder and depressive symptom scores were used as the outcome measures. RESULTS: The SNP-based heritability of major depressive disorder was 0.21 (SE = 0.02), the SNP-based heritability of depressive symptoms was 0.04 (SE = 0.01), and their genetic correlation was 1.001 (SE = 0.2). We found one genome-wide significant locus related to the broad depression phenotype (rs9825823, chromosome 3: 61,082,153, p = 8.2 × 10(-9)) located in an intron of the FHIT gene. We replicated this SNP in independent samples (p = .02) and the overall meta-analysis of the discovery and replication cohorts (1.0 × 10(-9)). CONCLUSIONS: This large study identified a new locus for depression. Our results support a continuum between depressive symptoms and major depressive disorder. A phenotypically more inclusive approach may help to achieve the large sample sizes needed to detect susceptibility loci for depression. %K CHARGE consortium, Depressive symptoms, FHIT gene, Genome-wide association study, Major depressive disorder, Psychiatric Genomics Consortium